Medial fibroplasia: involvement of renal artery and small renal arteries in renal vascular hypertension.

Dysplasia of the renal artery may cause renal vascular hypertension. The most common type of dysplasia is the medial fibroplasia. Medial fibroplasia, as well as the other types of dysplasia, has only been described in the main and primary branches of the renal artery. A case of medial fibroplasia, where arterial changes were seen far out in the small renal vessels is reported.

Pathology and pathophysiology of painful bladder diseases.

Painful bladder disease is an ill-defined disease presenting with chronic cystitis symptoms, despite sterile urine. This report includes only patients with painful bladder diseases of unknown etiology and pathogenesis. We have chosen to classify these patients pathoanatomically as follows: interstitial cystitis, detrusor myopathy, chronic unspecific cystitis and eosinophilic cystitis. The pathoanatomical appearance of the four groups of patients are described in details and certain clinical differences appear between the groups. The etiology and pathogenesis to the inflammatory reactions and muscle changes found in the detrusor biopsies are unknown, but many theories exist. It is suggested that something in the urine gains access to the bladder wall and initiates the pathoanatomical changes through a defective urothelium and glycosaminoglycans layer. In the interstitial cystitis patients, the inflammatory process and mast cell degranulation might be monitored by the urinary excretion of 1,4-methyl-imidazole-acetic acid and eosinophil cationic protein. It is concluded that no specific therapy for the disease exists, since etiology and pathogenesis are still unknown and therefore future research in this field is very important.

Skin reactions to urine in patients with interstitial cystitis.

Eight of 11 patients with interstitial cystitis had positive skin reactions to patch tests with urine (delayed type IV or irritant reactions). The positive reactions were seen to tests with the patients' own urine, but also, although less frequently, to tests with foreign urine as well. Immediate reactions (type I reactions; prick tests, scratch patch tests, and 20-minute patch tests) were not observed. The clinical morphology and the histology of the positive patch tests suggest a toxic rather than an allergic reaction, although the latter could not be totally excluded. The positive skin reactions may be relevant in the pathogenesis of interstitial cystitis suggesting a mucosal hyperreactivity to some component of urine.

Partial cystectomy for the myogenic decompensated bladder with excessive residual urine. Urodynamics, histology and 2-13 years follow-up.

Partial cystectomy was performed for myogenic decompensated bladder with excessive residual urine in 11 patients, in whom training instructions and pharmacological treatment were unsuccessful. Postoperatively, the patients were followed for 2-13 years (median 4 years). Both symptoms and residual urine were reduced permanently. Urodynamic testing had demonstrated underactive detrusor function in all. The supposed etiology was infravesical obstruction in 4, overdistension due to sensory bladder paresis in 3 and unknown in 4. Histological examination of the resected bladders showed focal degeneration of the smooth muscle cells (detrusor myopathy) in 7, transmural edema and vast deposits of collagen in 8, mastocytosis in 3 and eosinophilic cystitis in 1. In conclusion we regard partial cystectomy an alternative to clean intermittent self-catheterization in selected patients with excessive residual urine.

Autorosette inhibition factor: a positive acute phase reactant in interstitial cystitis.

Autorosette inhibition factor (AIF), complement C3d and eosinophil cationic protein (ECP) in urine were determined in 28 patients with painful bladder disease. In patients with interstitial cystitis (IC), diagnosed by the demonstration of detrusor mastocytosis, a positive correlation (r = 0.73, p less than 0.01) between AIF and C3d was found, whereas no reliable correlation was found in the remaining patients. The median concentration of urinary ECP was significantly elevated in the group of patients with IC whereas the median concentration of C3d was significantly elevated in both groups. AIF seems to behave as a positive acute phase reactant in IC. It is hypothesized that AIF may play a role in the pathogenesis of IC by influencing the normal barrier function of the epithelium of the bladder.

Painful bladder disease: clinical and pathoanatomical differences in 115 patients.

The diagnostic criteria for interstitial cystitis considered as a subgroup of painful bladder disease (that is sensory bladder disease and chronic abacterial cystitis) are not well established. Some urologists rely on symptoms, while others rely on cystoscopic appearance or pathological findings. Among 115 patients with painful bladder disease we compared symptoms, and cystoscopic and urodynamic findings in those with and without detrusor mastocytosis (28 or more mast cells per mm.2) and attempted to elucidate possible differences between the groups. We chose the pathological anatomical criterion of detrusor mastocytosis to be diagnostic for interstitial cystitis. A total of 43 patients had detrusor mastocytosis and other pathological anatomical signs of interstitial cystitis, and 72 had no mastocytosis but the pathological diagnoses of chronic unspecific cystitis, fibrosis of the bladder, detrusor myopathy, intestinal metaplasia and normal findings. When the 2 groups of patients were compared we found no differences in regard to symptoms (pain, dysuria, frequency, nocturia and urgency), frequency of allergy and hysterectomy, duration of symptoms, petechial bleeding during cystoscopy with bladder distension and cystometric findings. The patients with mastocytosis differed from those without mastocytosis in that they were older, and had a higher frequency of hematuria, a higher frequency of a red, scarred and richly vascularized bladder at cystoscopy before distension, and a smaller cystoscopic bladder capacity. We conclude that by dividing patients with painful bladder into 2 groups according to the mast cell counts in the detrusor, certain differences in the clinical findings in the groups can be ruled out. However, in individual patients one cannot note with certainty to which pathological anatomical group the patient belongs, since great overlapping between the groups exists. Whether only patients with detrusor mastocytosis have interstitial cystitis depends on definitions and still remains an open question.

A prospective double-blind clinically controlled multicenter trial of sodium pentosanpolysulfate in the treatment of interstitial cystitis and related painful bladder disease.

Painful bladder disease, sensory bladder disease, chronic abacterial cystitis and interstitial cystitis are ill-defined conditions of unknown etiology and pathogenesis, and, therefore, they are without any rational therapy. Pathogenetic theories concerning defects in the epithelium and/or mucous surface coat (including glycosaminoglycans) of the bladder, and theories concerning immunological disturbances predominate. Sodium pentosanpolysulfate (Elmiron) acts by substituting a defective glycosaminoglycan layer and inhibits complement reactions in inflammatory processes. We compared sodium pentosanpolysulfate versus placebo in a prospective double-blind, clinically controlled multicenter trial of 115 patients with painful bladder disease. Two protocols were used. Protocol A included 43 patients with clinically and pathologically anatomically verified interstitial cystitis (28 or more mast cells per mm.2), and protocol B included 72 patients with a painful bladder and unspecific histological findings. The patients were randomized to receive either sodium pentosanpolysulfate (200 mg. twice daily) or placebo capsules for 4 months. Before and after the trial the patients were evaluated with symptom grading, urodynamics and cystoscopy with distension and deep bladder biopsies. The results showed no difference between the pre-trial and post-trial values in the sodium pentosanpolysulfate and placebo groups in both protocols in regard to symptoms, urodynamic parameters, cystoscopic appearance and mast cell counts. A significant increase in the cystoscopically determined bladder capacity in the sodium pentosanpolysulfate group in protocol A was found. We conclude that no statistically or clinically significant effect of sodium pentosanpolysulfate was found compared to placebo in patients with painful bladder disease.

Vasoactive intestinal polypeptide concentration in human bladder neck smooth muscle and its influence on urodynamic parameters.

Three human studies were performed to evaluate the influence of vasoactive intestinal polypeptide (VIP) on bladder and urethral function. Bladder neck smooth muscle biopsies were obtained from nine men with functional bladder neck obstruction, from 10 men with medium sized benign prostatic hypertrophy and from four patients with a normal infravesical outlet. The biopsies were analysed for VIP by radioimmunoassay and by immunohistochemistry. No differences were found between the groups. Pressure-flow-EMG studies were performed in five men and urethrocystometry was performed in six women at rest, repeated coughing and at squeezing before, during and after VIP 3 micrograms/kg X h intravenously. No systematic changes developed in any of the urodynamic parameters.

Urine eosinophil cationic protein in painful bladder disease.

Urine eosinophil cationic protein (U-ECP), blood eosinophils and eosinophils in bladder biopsy specimens were studied in 30 patients with painful bladder disease (15 with detrusor mastocytosis, i.e. interstitial cystitis (IC) (greater than or equal to 28 mast cells/mm2 in the detrusor muscle) and 15 patients without detrusor mastocytosis). In patients with IC the median concentration of U-ECP was 140 arbitrary u/l versus 14 arb. u/l in the remaining patients (P less than 0.001). The mean peripheral leukocyte count was significantly lower in the IC group (P less than 0.05). Tissue infiltration with eosinophils was found in 43% of the bladder biopsies from patients with IC compared with 4% of the biopsies in the remaining patients (P less than 0.05). A negative correlation between peripheral eosinophils and U-ECP was found in the patients with IC (r = 0.52, P less than 0.05). These results suggest that eosinophils are attracted to the inflammatory site in the bladder wall where ECP is released. Eosinophils thus seem to participate actively in the inflammatory process. U-ECP seems to provide valuable diagnostic information when diagnosing IC in patients with painful bladder disease. It is suggested that ECP might be involved in the process of tissue destruction in IC.

Urinary excretion of a metabolite of histamine (1,4-methyl-imidazole-acetic-acid) in painful bladder disease.

Thirteen patients with interstitial cystitis (detrusor mastocytosis) and 12 other patients with painful bladder disease without mastocytosis collected 24-h urine specimens that were analysed for the major metabolite of histamine, 1,4-methyl-imidazole-acetic-acid (1,4-MIAA), by reversed phase ion-pair high performance liquid chromatography. The median urinary excretion of 1,4-MIAA was 3.34 mg/24 h (range 1.47-4.66) in the patients with detrusor mastocytosis and 1.75 mg/24 h (range 0.18-4.30) in the other patients with a painful bladder (P less than 0.01). It was concluded from this study that patients with a painful bladder and detrusor mastocytosis had a significantly elevated urinary excretion of 1,4-MIAA compared with other painful bladder patients without mastocytosis, whose urinary excretion of 1,4-MIAA was within the normal range (0.72-2.34 mg/24 h). We suggest that the urinary excretion of 1,4-MIAA might be useful in the diagnosis of interstitial cystitis.

Chronic cystitis: excretion of epidermal growth factor (EGF)/urogastrone (URO).

To investigate the role of epidermal growth factor (EGF)/urogastrone (URO) in the cytoprotection of the urothelium in the urinary bladder we measured the concentration of EGF/URO by radioimmunoassay in urine from patients with chronic cystitis. The series comprised 12 patients with classical interstitial cystitis, 10 young females with recurrent bacterial cystitis and 12 children with recurrent cystitis together with sex- and age-matched controls. The results showed no variation in the substance concentration of EGF/URO in urine from cystitis patients and control groups. A negative correlation was found between 1) the urinary concentration of EGF/URO and increasing age, and 2) the excretion of EGF/URO per mol creatinine. The present study did not show a decreased output of EGF/URO in patients with chronic cystitis. Further studies are necessary in the evaluation of the physiological role of EGF/URO in the urinary tract.

Ultrasonographic diagnosis of renal stones.

To illucidate the diagnostic accuracy of ultrasound in the detection of renal stones we performed a blind comparative study of ultrasonography and i.v. urography. In 92 kidneys with 58 stones, 10 stones smaller than 6 mm were overlooked by ultrasound, whereas all stones 6 mm or larger were correctly detected. In one case of uric acid stone disease i.v. urography was inconclusive in determining the true nature of a renal pelvic filling defect, whereas ultrasound correctly diagnosed a stone. We conclude that ultrasonography has a place in diagnosis and control of renal stones.

Electron microscopic investigation of the bladder urothelium and glycocalyx in patients with interstitial cystitis.

The electron microscopic appearance of the bladder urothelium and glycocalyx was investigated in ten patients with well defined interstitial cystitis and compared to the findings in ten control patients with stress incontinence as the only symptom. Ruthenium red, a polycationic dye which binds specifically to cell surface acid polysaccharides, was used to demonstrate the glycocalyx. In cases of interstitial cystitis two types of luminal cell were observed, each possessing a distinct surface glycocalyx. One type of cell possessed numerous plaques of asymmetric unit membrane associated with a relatively thin glycocalyx. The second type of cell was characterised by numerous microvilli and a relatively thick glycocalyx. In control material each type of cell and its associated glycocalyx was identified with similar frequency. Our study concludes that there are no differences in the morphologic appearances of the glycocalyx and of urothelial cells in patients with interstitial cystitis when compared with controls. Hence, the hypothesis that an important pathogenic factor in interstitial cystitis is a defective glycocalyx associated with a permeable urothelium, has not been supported.

The AMS artificial urinary sphincter on the bulbous urethra.

An artificial sphincter with the cuff on the bulbous urethra was implanted in 29 patients with urinary incontinence. After a median observation time of 3 years, 19 patients were continent, four others were improved and the system had been removed in six cases. Urethral erosion occurred in only two cases, both due to infection. Use of low-pressure systems is recommended.